Multi-drug resistant Acinetobacter (MDRA) Surveillance and Control

Alison Holmes

• The organism and it’s

epidemiology

• Surveillance

• Control

What is it?

What is it?

What is it?

What is it?

Acinetobacter : The organism

• Aerobic, Gram-negative bacterium, non motile, non fermenting,

coccobacillus in stationary phase, rod shaped in rapid growth, forms

biofilms and survives environmental dessication for weeks.

• Began to be recognised in 1970s as an opportunistic hospital

pathogen, causing outbreaks

• A. baumanii >80% infections

• Infections in ICUs, ventilated patients, burns units

•Pneumonia

•Bacteraemia

•Osteomyelitis (trauma/deep wound infection)

• Can cause fatal infections in debilitated patients

•Historically, a pathogen of humid climates.

• Since the 1970s, an increasingly common nosocomial problem in

temperate climates- where seasonal variation seen

•Years before a concern in ICUs in the US, it was cited as the cause of 17

% of cases of VAP in a Guatemalan ICU

•Most common cause of Nosocomial pneumonia in tertiary care hospitals

in Thailand (Werarak P et al Feb 2012)

•Ability to accumulate diverse mechanisms of resistance and emergence

of highly resistant strains

•Dramatic clonal outbreaks of MDRA have

occurred across the world, some involving

multiple hospitals

Multiple mechanisms of antibiotic resistance

• Constitutive or acquired via plasmids, integrons, and transposons.

• Methods include:

1.enzymatic inactivation of antibiotic

2.modification of antibiotic target sites,

3.expression of efflux pumps or down regulation porin

channel expression.

• Resistance to β-lactams primarily caused by β-lactamase production, including

extended spectrum β-lactamases, metallo- β-lactamases and most commonly,

oxacillinases (OXA)…which have carbapenemase activity

• Antibiotic target site alterations confer resistance to fluoroquinolones (gyrA,

parC) and aminoglycosides (arm, rmt), and to a much lesser extent, β-lactams.

• Efflux pumps contribute to resistance against β-lactams, tetracyclines,

fluoroquinolones, and aminoglycosides.

• Porin channel deletion contribute to β-lactam resistance and may contribute to

rarely seen polymyxin resistance.

• In UK - prior to 2000, virtually all A. baumannii isolates were

susceptible to carbapenems and very few genotypes

appeared to occur in multiple hospitals. These patterns

changed with the multicentric isolation of the SE clone, with its

variable resistance to imipenem and meropenem.

• The spread of two OXA-23-producing clones represent a

further ratcheting of the problem, being more consistently

resistant to carbapenems

• Emergence of A. baumanii related in part to survival ability

and rapid development of resistance to all major antibiotic

classes

Summary of the

distribution and

genetic context of

the OXA-type

enzymes in

Acinetobacter

baumannii.

Peleg A Y et al. Clin. Microbiol. Rev. 2008;21:538-582

Common misconceptions…

• ‘ubiquitous in nature’

• ‘recovered easily from soil,

water, animals’

• ‘frequent skin* and oro-

pharyngeal coloniser’*

This may apply to other members of the genus Acinetobacter ..

But not A. baumanii (and its close relatives of clinical importance)

*But the in tropics situation e.g. HK 53 % medical students hands carried A.

baumanni in summer. Chu Y W et al ‘99 J Clin Micro 37,

Factors facilitating Spread

Towner KJ JHI 2009

Factors facilitating Spread

Towner KJ JHI 2009

‘Iraqibacter’

MDRA and Military

• Wounds and burns, bacteraemias

• High throughput, influx of trauma

• High levels broad spectrum antibiotics

for trauma injuries

• Little de-escalation or microbiology support

• Antibiotic prescribing intense and without policy

• Much equipment, much contaminated

• Multiple transfers through different units in medical evacuation

• Many procedures along the routes

• MDRA isolated in every hospital on the aeromedical evacuation routes from

Iraq and Afghanistan. Spread in units where repatriated

• High pressure lavage…aerosol generating

• Not pre-injury colonisation or inoculation at time of trauma

• Hospital unit is the habitat

• Periodic closures of units/tents for deep clean

• MDRA led to major focus of military on infection control, microbiology

support, antibiotic programme …… and MDRA control

Multi-drug resistant Acinetobacter (MDRA)

• Over the past few decades, isolates of Acinetobacter spp. have

successfully accumulated resistance to penicillins, cephalosporins,

quinolones and aminoglycosides

•Between 2003 and 2006, two carbapenemase-resistant strains (SE

clone and OXA-23) became prevalent in over 40 UK hospitals

• OXA-23 clone susceptible only to colistin

• SE clone susceptibility to carbapenems is variable

• predominantly in the London area

• isolates originated mainly from sputum and wound cultures

• majority from patients in intensive care units

Coelho JM, et al. J Clin Microbiol. 2006; 44:3623-3627

Turton JF, et al. J Hosp Infect., 2004; 58: 170-179

• National-level A. baumannii resistance

to carbapenems grew nearly eight times,

going from 5.2% in 1999 to 40.8% in

2010 and increasing in all but one years

during the period.

• The largest and most consistent

increase came from the Midwest (East

North and West South Central ),

followed by the South Atlantic and

Pacific states.

• Because of Acinetobacter’s low virulence,

few colonized patients develop a disease.

However, when an infection does occur, it

often results in hospital-wide outbreaks and

relatively high rates of mortality. In the

outpatient setting, the pathogen has been

associated with wound infections among

soldiers, earning it the name “Iraqibacter.”

• The striking decline in carbapenem

effectiveness points to two major

conclusions: one is the urgent need to

develop new drugs active against Gram-

negative bacteria; second is the medical

community’s need to evaluate the benefits of

large-scale vaccination of populations most

affected by A. baumannii, such as military

personnel and those in contact with them.

Surveillance

Surveillance in UK

Voluntary surveillance by diagnostic laboratories to the

Health Protection Agency (HPA)

• All Acinetobacter spp.

• Reporting of cases via electronic data transfer system to central

database

HPA Voluntary Surveillance: Data Analysis

• For A. baumannii, there has been a significant rise

in imipenem resistance from 21% in 2006 to 27% in

2010 (p<0.05)

• Only a small proportion of all isolates were tested.

• Between 2007 and 2011 there were no significant

changes.

http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317131514188

HPA Voluntary Surveillance: Data Analysis

• Antibiotic susceptibility data for reports of A. baumannii bacteraemia, England, Wales, and Northern Ireland: 2006 to 2010

2006 2007 2008 2009 2010

Total reports 413 415 295 219 212

Ciprofloxacin Non-susceptible 36% 31% 29% 27% 22%

Reports with susceptibility data 319 338 243 177 154

Imipenem Non-susceptible 21% 26% 30% 30% 27%

Reports with susceptibility data 126 183 108 91 56

Meropenem Non-susceptible 35% 24% 29% 14% 23%

Reports with susceptibility data 175 186 159 119 109

Ceftazidime Non-susceptible 70% 68% 72% 74% 75%

Reports with susceptibility data 233 272 186 155 134

Adapted from http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317131514188

Surveillance cont…

British Society for Antimicrobial Chemotherapy (BSAC)

• Respiratory Resistance Surveillance Programme

• Sentinel surveillance

• All Acinetobacter spp., identified to species level

• Hospital-acquired infections

• Lower respiratory tract specimens, from patients with clinical infection

• Susceptibility testing against variety of antimicrobials

Antimicrobial Resistance and Healthcare Associated Infections

Reference Unit (HPA)

• reference unit available for confirmation of “unusual” resistance

patterns

• Acinetobacter spp. isolates can be sent if they exhibit resistance to

carbapenems or colistin

Outbreak Detection

• At national and regional level, Acinetobacter spp. included in LabBase

Exceedance Reporting performed weekly at the HPA

• MDRA not distinguishable

• Outbreak detection not available specifically, further investigation

required

Need

standardised

definitions for

surveillance

and outbreak

detection

Need for Standard Definitions

Clin Microbiol Infect 2012; 18: 268–281

Clin Microbiol Infect 2012; 18: 268–281

Clin Microbiol Infect 2012; 18: 268–281

However……outside the lab…..

• Need pragmatic definitions for surveillance and for

clinicians…

• Carbapenem resistance ?

• What about ‘CRAB’ ?

• See CDDEP ( )

• Drug/Bug surveillance

• Useful as a definition....?

• Can be CRAB without being MDRA...

• Addresses importance of OXA type carbapenemase

• And clinical significance ‘resistance to critically important

drug class’

The Control

Potential Sources in Hospital Environment

Infection Control

Key measures include:

• Patient contact-isolated in side-room

• Careful review of practice

• More than one case, outbreak

management

• Typing

• Cohorting patients, nursing staff.

• Antimicrobial prescribing reviewed

• Strict hand hygiene practices

• Implementation of “deep clean”

strategies;

• Close attention to environment and all

equipment

Infection Control

• Ward closures often required

• Followed by terminal clean before re-open

• Most significant source in an outbreak situation are patients already

infected/colonised with MDRA

• The importance of adequate staffing needs to be addressed

• Once endemic in a healthcare setting, MDRA is difficult to eradicate

Detailed guidelines on how to deal with MDRA outbreaks prepared by a Working

Party of the HPA http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1194947325341

• Avoid homogeneity of

prescribing

• Minimise

carbapenem use

Novel Strategies needed

• A. baumannii poses a particular challenge due to the

intrinsic drug resistance imparted by its impermeable

outer membrane and its rapid acquisition of resistance

to new antibiotics

• Given these characteristics, small molecule antibiotics

will unlikely prove to be a lasting solution to A.

baumannii infections.

• Novel strategies for the treatment and prevention of

these infections are therefore desperately needed.

Whole Genome Sequencing

• Genomic

epidemiology

• Disruptive

technology

• Several

technologies on the

market

• Determine chains of

transmission

• Target intervention

• Pallen ‘’JHI was a

scoping study’’

The Importance of closure

Needs adequate

risk assessment

and cost

effectiveness

analysis.

What are the

health economic

implications?

CID 2012:55 (11): 1589-90 Apisarnthanarak, Li Yang, Warren